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Tony Gould
WHO reference
WHO Technical Report Series, No. 937, 2006 - Annex 2 "Supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms" Comprehensive guide May also be applied to other dosage forms Not intended to be prescriptive risk principles apply
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HVAC
Objectives
To understand key issues in commissioning, qualification and maintenance of HVAC systems
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HVAC
Documentation requirements to assist in commissioning, qualification and maintenance
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Description of design, installation and functions Specifications, requirements Manuals Operating procedures Instructions for performance control, monitoring and records Maintenance instructions and records Training of personnel program and records
HVAC
Commissioning
Precursor to qualification Includes setting up, balancing, adjustment and testing of entire HVAC system to ensure it meets requirements in URS and capacity Acceptable tolerances for parameters Training of personnel
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HVAC
Commissioning (2)
Records and data maintained include: Installation records documented evidence of measure capacities of the system Data: Design and measurement for e.g. air flow, system pressures O&M manuals, schematic drawings, protocols, reports
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HVAC
Qualification
Validation is an extensive exercise Qualification of the HVAC system is one component in the overall approach that covers premises, systems/utilities, equipment, processes etc. See also full guidelines on "Validation" in WHO TRS No 937, 2006, Annex 4. Risk based approach for HVAC qualification
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HVAC
Qualification (2)
Described in a Validation Master Plan (VMP) VMP to include the nature and extent of tests, and protocols DQ, IQ, OQ, and PQ Risk analysis to determine critical and non-critical parameters, components, sub-systems and controls
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HVAC
Qualification (3)
Direct impact components and critical parameters should be included Non-critical systems and components are subjected to Good Engineering Practices (GEP) Acceptance criteria and limits defined in design stage Design conditions, normal operating ranges, operating ranges, alert and action limits
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HVAC
Design conditions and normal operating ranges set to achievable limits OOS results recorded
N A C T I O A N L I M L E R T I T L I M I T A L E R T A C L I M T I O I T N
e s ig n
o n d it io n
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p e r a t in g
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p e r a t in g
a n g e
a lid a t e d
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HVAC
Qualification examples of aspects to consider
DQ Design of the system, URS
(e.g. components, type of air treatment needed, materials of construction)
IQ Verify installation
E.g. relevant components, ducting, filters, controls, monitors, sensors etc Includes calibration where relevant
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HVAC
Qualification (7)
Tests performed according to protocols and procedures for the tests Results recorded and presented in report (source data kept) Traceability e.g. devices and standards used, calibration records; and conditions specified
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HVAC
Qualification (6)
Conduct of the tests: Time intervals and procedure to be defined by the manufacturer Influenced by the type of facility and level of protection See also ISO 14644 for methods of testing Re-qualification, and change control
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HVAC
Qualification (4)
Typical parameters to be included in qualification (based on risk assessment): Temperature Relative humidity Supply, return and exhaust air quantities Room air change rates Room pressures (pressure differentials)
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PQ Workshop, Abu Dhabi | October 2010
HVAC
Qualification (5)
Typical parameters to be included in qualification (based on risk assessment) (2): Room clean up rate Particulate matter, microbial matter (viable and non-viable) HEPA filter penetration tests Containment system velocity Warning/alarm systems
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PQ Workshop, Abu Dhabi | October 2010
HVAC
Schedule of tests to demonstrate continuing compliance
Test Parameter
Particle count test
Objective
Verifies cleanliness
6 months or 12 months Particle counter. depending on Class Readings and positions 12 months Measure pressure difference Measure supply and return air, calculate air change rate Velocity measurement
Airflow velocity
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HVAC
Recommended optional strategic tests
Test Parameter
Filter leakage Containment leakage Recovery (time)
Objective
Verify filter integrity Verify absence of cross-contamination Verify clean-up time
Airflow visualization
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HVAC
Cleanroom monitoring program (1)
Routine monitoring program as part of quality assurance Additional monitoring and triggers e.g. Shutdown Replacement of filter elements Maintenance of air handling systems Exceeding of established limits
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HVAC
Cleanroom monitoring program (2) Particles and Microbiological contaminants
q Number of points/locations for monitoring determined, q q q q q
specified, documented in procedure and or protocol Sufficient time for exposure, and suitable sample size Identification and marking of sampling points Definition of transport, storage, and incubation conditions Results to reflect the procedure/protocol followed Define alert and action limits as a function of cleanliness zone/class
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HVAC
Cleanroom monitoring program (3)
Cleanrooms should be monitored for micro-organisms and particles
air
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HVAC
Definition of Conditions
as built
air
at rest
air
in operation
air
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HVAC
Qualification examples of aspects to consider in qualification (OQ, PQ)
Test Uni-directional airflow / LAF 2 N/A 2, 3 2 2 2 Turbulent / mixed airflow 2 2, 3 Optional 2 N/A 3 1 := As built (ideally used to perform IQ) 2 = At rest (ideally used to perform OQ) 3 = Operational (ideally used to perform PQ) Airflow volume / rate Parallelism Air flow pattern Description
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HVAC
Qualification examples of aspects to consider in qualification (OQ, PQ)
Description 1 := As built (ideally used to perform IQ) 2 = At rest (ideally used to perform OQ) 3 = Operational (ideally used to perform PQ)
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HVAC
Maintenance
Procedure, program and records for planned, preventative maintenance
E.g. Cleaning of filters, calibration of devices
Appropriate training for personnel Change of HEPA filters by suitably trained persons Impact of maintenance on:
Product quality Qualification
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HVAC
Inspecting the air handling system
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Verification of design documentation, including description of installation and functions specification of the requirements Operating procedures Maintenance instructions Maintenance records Training logs Environmental records Discussion on actions if OOS values On site verification (walking around the site)
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HVAC
Conclusion
Air handling systems:
q q q
Play a major role in the quality of pharmaceuticals Should be designed properly, by professionals Should be treated as a critical system
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